Investigation of the abasic sites induced by hydrogen peroxide and methyl methanesulfonate in calf thymus DNA and BEAS-2B cells.

Autor: Dinh DT; Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung 402, Taiwan; Department of Environmental Engineering, National Chung Hsing University, Taichung 402, Taiwan., Bahari GP; Department of Environmental Engineering, National Chung Hsing University, Taichung 402, Taiwan., Xu Q; Department of Environmental Engineering, National Chung Hsing University, Taichung 402, Taiwan., Wei CH; Department of Environmental Engineering, National Chung Hsing University, Taichung 402, Taiwan., Chen DR; Comprehensive Breast Cancer Center, Changhua Christian Hospital, Changhua 500, Taiwan., Hsieh WC; Department of Laboratory Medicine, Da-Chien General Hospital, Miaoli 360, Taiwan., Lin PH; Department of Environmental Engineering, National Chung Hsing University, Taichung 402, Taiwan; Research Center of Environmental Education and Sustainable Technology, Nantou 540, Taiwan. Electronic address: pohsiunglin@yahoo.com.
Jazyk: angličtina
Zdroj: Toxicology letters [Toxicol Lett] 2024 Nov; Vol. 401, pp. 101-107. Date of Electronic Publication: 2024 Sep 24.
DOI: 10.1016/j.toxlet.2024.09.008
Abstrakt: The primary goals of this study were to investigate the formation of abasic sites (AP sites) induced by methyl methanesulfonate (MMS) and hydrogen peroxide (H 2 O 2 ), and to characterize specific types of these pro-mutagenic DNA lesions in calf thymus DNA (CT-DNA), and BEAS-2B human lung normal cell line. Furthermore, these profiles were compared with those observed in leukocytes derived from healthy controls (HC), breast cancer patients (BCP) before treatment, and 5-year survivors. Results indicated that both H 2 O 2 and MMS induced the concentration- and time-dependent formation of AP sites in CT-DNA. To characterize the specific types of AP sites induced by H 2 O 2 or MMS, we performed AP site cleavage assay using putrescine, T7 exonuclease (T7 Exo), and exonuclease III (Exo III). Results showed that the AP sites induced by H 2 O 2 in CT-DNA were predominantly 5'-and 3'-nicked AP sites and no intact AP sites were detected. By contrast, the majority of AP sites generated by MMS in CT-DNA are not excisable and are classified as residual and intact AP sites. Similar approaches were performed in human BEAS-2B cells and comparable observations were confirmed in the cell-based model. Further investigation indicated that the profile of the AP sites observed in Taiwanese HC is identical to that of BEAS-2B cells treated with H 2 O 2 whereas the pattern of AP sites detected in BCP is similar to that of CT-DNA exposed to H 2 O 2 , suggesting that these AP sites were produced primarily through reactive oxygen species (ROS) generation. More than 70 % of the AP sites in leukocytes derived from BCP were 5'-nicked and residual AP sites. Furthermore, the characteristics of the AP sites detected in 5-year survivors are comparable with the ones in HC by using putrescine cleavage assay. Overall, we speculate that deficiency in the DNA repair cascade may play a role in mediating the formation of specific types of AP sites detected in BCP.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Po-Hsiung Lin reports financial support was provided by National Science and Technology Council. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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